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Genomes of the Mouse Collaborative Cross.

Anuj Srivastava1, Andrew P Morgan2,3,4, Maya L Najarian5

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Summary

The Collaborative Cross mouse panel genomes were sequenced, revealing thousands of new genetic variants due to mutation and selection. This resource enhances genetic experiments and provides insights into mouse genome evolution.

Keywords:
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Area of Science:

  • Genomics
  • Animal Models
  • Bioinformatics

Background:

  • The Collaborative Cross (CC) is a multiparental recombinant inbred (RI) mouse panel crucial for genetic research due to its stability and reproducibility.
  • Previous genome characterization relied on haplotype reconstructions, which had limitations in resolution and founder assignment accuracy.

Purpose of the Study:

  • To present whole-genome sequences for 69 CC strains as a resource for genetic research.
  • To improve the resolution and completeness of CC strain genomes.
  • To investigate the impact of mutation and selection on CC genome evolution.

Main Methods:

  • Whole-genome sequencing of 69 CC strains using paired-end short reads at 30× coverage.
  • Comparative analysis of sequenced genomes with previous haplotype reconstructions and founder strain genomes.
  • Analysis of genetic variation, including SNPs, mutations, and large deletions.

Main Results:

  • Sequencing substantially improved the fine structure and completeness of CC strain genomes.
  • Identified tens of thousands of new genetic variants, including SNPs and large deletions, introduced by mutation and drift.
  • Observed significant reduction in haplotype frequencies from wild-derived strains (CAST/EiJ, PWK/PhJ) and evidence of selection against these founders.
  • Estimated SNP mutation accumulation rate at 2.4 ± 0.4 per gigabase per generation.

Conclusions:

  • The sequenced CC genomes provide a critical resource for users, enhancing the power and interpretation of genetic experiments.
  • The study highlights the role of mutation and selection in shaping the genomes of common research resources.
  • The findings offer insights into the evolutionary processes acting on inbred mouse strains.